Structural basis of the interaction between integrin α6β4 and plectin at the hemidesmosomes |
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| Authors: | José M de Pereda M Pilar Lillo Arnoud Sonnenberg |
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| Institution: | 1. Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas—Universidad de Salamanca, Campus Unamuno, Salamanca, Spain;2. Departamento de Biofísica, Instituto de Química Física Rocasolano, Consejo Superior de Investigaciones Científicas, Serrano, Madrid, Spain;3. Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan, CX Amsterdam, The Netherlands |
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| Abstract: | The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane. We describe the crystal structure at 2.75 Å resolution of the primary α6β4–plectin complex, formed by the first pair of fibronectin type III domains and the N‐terminal region of the connecting segment of β4 and the actin‐binding domain of plectin. Two missense mutations in β4 (R1225H and R1281W) linked to nonlethal forms of epidermolysis bullosa prevent essential intermolecular contacts. We also present two structures at 1.75 and 2.05 Å resolution of the β4 moiety in the absence of plectin, which reveal a major rearrangement of the connecting segment of β4 on binding to plectin. This conformational switch is correlated with the way α6β4 promotes stable adhesion or cell migration and suggests an allosteric control of the integrin. |
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| Keywords: | cell adhesion epidermolysis bullosa hemidesmosome integrin plakin |
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